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Biomedical subjects

S Cook

Publications and source records attributed to S Cook.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cerebral oedema following intracerebral haemorrhage: the effect of the NMDA receptor antagonists MK-801 and D-CPPene.

The effects of pre-treatment with the NMDA receptor antagonists MK-801 and D-CPPene on the development of brain oedema were investigated in a rodent model of intracerebral haemorrhage. In acute experiments (4 hour survival) both drugs caused significant hypotension and had significant anaesthetic effects whilst conferring no protection against oedema formation. In chronic experiments (24 hour survival) MK-801 conferred no protection against brain oedema. With D-CPPene marginal protection against cortical oedema may have been conferred but this result should be interpreted with caution.

Animals↗
PubMed1994

Intrinsic and extrinsic characteristics of human tumors relevant to radiosurgery: comparative cellular radiosensitivity and hypoxic percentages.

UNLABELLED: We have collected the in vitro x-ray radiation survival characteristics of 181 lines from 12 different classes of exponentially growing human tumor cells (sarcomas, lung cancers, colo-rectal cancers, medulloblastomas, melanoma, breast cancers, prostate cancers, renal cell cancers, grades III and IV brain tumors, ovarian, and head and neck cancers). This information was used to intercompare survival after single high doses of 20-40 Gy for each tumor line. Radiosensitivities could roughly be divided into two groups. The more radiosensitive group included: sarcoma, small-cell lung cancer, non-small cell lung cancer, colorectal cancer, medulloblastoma and melanoma. The more radioresistant group included breast, prostate, renal cell, primary brain tumors, ovarian tumors, and head and neck cancers. Using a model of a 3 cm diameter brain lesion containing about 1.4 x 10(9) oxic cells, the single doses calculated to reduce survival to 1 cell were: sarcoma and small cell lung cancers-22-23 Gy; melanoma-25 Gy; non-small cell lung and colorectal cancer-26 Gy; medullo-blastoma-28 Gy; breast, prostate, renal cell, primary brain tumors, ovarian tumors, and head and neck cancers-30-36 Gy. If, however, tumors contained on average 20 percent hypoxic cells, the dose needed for equivalent cell killing increased by about a factor of 2.6-2.8. Also, there was no correlation between the ranking of relative radiosensitivities of the various classes of tumor cells at high doses (as in radiosurgery) to the sensitivity at low doses (as in conventional fractionated radiotherapy). CONCLUSION: available information on the intrinsic radiosensitivity of human tumor cells indicates that meaningful differences exist among different histological classes of neoplasm that are relevant to the single high doses used in radioneurosurgery, and which could constitute a basis for "tailoring" the administered dose to the particular neoplasm. However, if intracerebral lesions contain a large number of hypoxic cells (e.g., 20%), this may constitute a significant problem.

Cells, Cultured↗
PubMed1994

Stages leading to and following fusion of sperm and egg plasma membranes.

The site of gamete interaction of electrophysiologically recorded Lytechinus variegatus eggs, fixed with osmium tetroxide (OsO4) and/or glutaraldehyde (GTA) at varying intervals after the onset of the increase in membrane conductance induced by an attached sperm, has been examined by high-voltage and conventional transmission electron microscopy. Although GTA and a GTA-OsO4 mixture induced different electrical responses, specimens prepared with the two fixatives were ultrastructurally similar. In specimens observed within 5 s of the change in conductance, the acrosomal process projected through the vitelline layer and abutted the egg plasma membrane. A conspicuous layer of bindin surrounded the acrosomal process and connected the sperm to the egg's vitelline layer. In a fortuitous specimen fixed within 4 s following the change in conductance, the area of contact between the gamete plasma membranes possessed a trilaminar structure that separated the egg's and sperm's cytoplasms. The morphology of this area of contact was consistent with previously proposed intermediates of membrane fusion. Five to six seconds after the change in conductance, the sperm was connected to the egg via a narrow cytoplasmic bridge that consisted of the former acrosomal process and a projection of the egg cortex. The region of the bridge midway between the fused gametes was encircled by dense material that marked the site of sperm-egg fusion. Gamete interactions in which the activation potential was recorded (unclamped egg) were comparable in time and ultrastructure to events taking place in voltage-clamped eggs except for one major difference. Intact cortical granules (one to three) were observed beneath the tip of the incorporating sperm in unclamped eggs fixed following the onset of the activation potential, whereas all cortical granules dehisced in clamped eggs.

Animals↗
PubMed1993

Cotrel-Dubousset instrumentation. Results in 52 patients.

Fifty-two posterior spinal fusions were performed for pediatric idiopathic, congenital, and neuromuscular scoliotic curves. Cotrel-Dubousset instrumentation was used in all patients. Nine had prior anterior spinal releases and fusions. The patterns were mixed, with a predominance of right thoracic curvatures. The average preoperative curve measured 60.6 degrees, with correction to 29. Seven patients required revision surgery, and 17 wore orthoses after operation. There were 17 complications in this group, including hook pullout, prominent hardware, infection, pseudarthrosis, and two cases of broken Cotrel-Dubousset instrumentation rods. Fatigue failure of this instrumentation, secondary to pseudarthrosis, has not been reported previously, and these two cases are presented in detail. The operative morbidity and difficulty were increased in the larger idiopathic curves and in neuromuscular and congenital scoliosis. Cotrel-Dubousset instrumentation is an overall excellent tool for the multiplanar correction of scoliosis and is amenable to revision surgery.

Adolescent↗
PubMed1993

Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease).

Pathological studies of mice homozygous for the motor neuron degeneration (Mnd) mutation show abnormalities similar to those of the human neuronal ceroid lipofuscinoses: sudanophilic, autofluorescent intraneuronal inclusions that are immunoreactive with antibodies to subunit c of mitochondrial ATP synthase. Ultrastructurally, the inclusions have the pentalaminar structure characteristic of some form of human neuronal ceroid lipofuscinosis and of canine and ovine models of neuronal ceroid lipofuscinosis. Similar inclusions are observed in many somatic organs and in the retina, which develops photoreceptor degeneration. This mutation, previously considered a model of amyotrophic lateral sclerosis, may be a useful model for molecular and genetic studies of human neuronal ceroid lipofuscinosis because mice have been well characterized genetically. Since they are inexpensive to breed and maintain, they can also be used to test therapeutic interventions.

Animals↗
PubMed1993

Effective use of a strategy using assigned red cell units to limit donor exposure for neonatal patients.

Critically ill neonatal infants receive frequent small-volume red cell (RBC) transfusions for replacement of blood drawn for laboratory analysis or for treatment of symptomatic anemia secondary to underlying medical conditions and/or a relative bleeding diathesis. Retrospective review of transfusion practice in a hospital revealed that the donor exposure-to-transfusion ratio was 1:1.3. In an effort to limit donor exposure and decrease the risk of transfusion-transmitted disease, a sterile connection device was used for multiple small-aliquot preparations. Three neonatal infants were given part of the same RBC unit, and the assigned RBC unit was used only until it reached 14 days of age. These criteria resulted in 49-percent reduction in donor exposure for neonatal infants weighting less than 1500 g and 27-percent reduction for those weighing more than 1500 g. The donor exposure-to-transfusion ratio decreased to 1:2.5. RBC waste from syringe aliquot preparation and residual volume at Day 15 were a mean of 32 percent of the total unit volume. Of 722 transfusion occurrences, there were no reported adverse effects due to elevated potassium subsequent to transfusion of 14-day-old RBCs. This limited-donor-exposure strategy effectively meets the needs of a transfusion service and will reduce the donor exposures of neonatal infants in similar institutions.

Blood Component Transfusion↗
PubMed1993

Proteus mirabilis fimbriae: N-terminal amino acid sequence of a major fimbrial subunit and nucleotide sequences of the genes from two strains.

Proteus mirabilis, a common cause of urinary tract infection in hospitalized and catheterized patients, produces mannose-resistant/klebsiella-like (MR/K) and mannose-resistant/proteus-like (MR/P) hemagglutinins. The gene encoding the major structural subunit of a fimbria, possibly MR/K, was identified in two strains. A degenerate oligonucleotide probe based on the N terminus of the Proteus uroepithelial cell adhesin and antiserum raised against the denatured polypeptide were used to screen a cosmid gene bank of strain HU1069. A cosmid clone that reacted with the probe and antiserum was identified, and a fimbria-like open reading frame was determined by nucleotide sequencing. The predicted N-terminal amino acid sequence of the processed polypeptide, ENETPAPKVSSTKGEIQLKG (residues 23 to 42), did not match the uroepithelial cell adhesin N terminus but, rather, matched exactly the N-terminal amino acid sequence of a polypeptide with an apparent molecular size of 19.5 kDa isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of a fimbrial preparation from strain HI4320 expressing MR/K hemagglutinin. By using an oligonucleotide from the HU1069 open reading frame, the fimbrial gene was isolated and sequenced from a cosmid gene bank clone of strain HI4320. A 552-bp open reading frame predicts a 184-amino-acid polypeptide including a 22-amino-acid hydrophobic leader sequence. The unprocessed polypeptide is predicted to be 18,921 Da; the processed polypeptide is predicted to be 16,749 Da. The predicted amino acid sequence of the polypeptide encoded by the gene, designated pmfA, displayed 36% exact matches with the mannose-resistant fimbrial subunit encoded by smfA of Serratia marcescens but only 15% exact matches with the predicted sequence encoded by mrkA of Klebsiella pneumoniae.

Amino Acid Sequence↗
PubMed1993

Identification of Mycobacterium tuberculosis DNA in five different types of cutaneous lesions by the polymerase chain reaction.

BACKGROUND AND DESIGN: A spectrum of skin lesions are believed to be secondary to the presence of Mycobacterium tuberculosis. Demonstration of M tuberculosis directly or in culture in some of these eruptions can be difficult. We used the polymerase chain reaction and a primer/probe set specifically for M tuberculosis complex DNA to evaluate five types of skin lesions clinically considered to represent infection by, or reaction to, M tuberculosis. OBSERVATIONS: Mycobacterium tuberculosis DNA was demonstrated in paraffin-embedded sections of these five cases, representing a variety of clinical and histologic patterns. In two cases, M tuberculosis could not be demonstrated by routine cultural methods. CONCLUSION: DNA diagnostic methods such as the polymerase chain reaction can be used to rapidly identify cutaneous lesions produced by M tuberculosis.

Adult↗
PubMed1992

Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype.

OBJECTIVE: To define the clinical spectrum of glucocorticoid-remediable aldosteronism (GRA) in a large kindred. DESIGN: Screening all at-risk relatives of a proband for GRA using a specific biochemical phenotype and collecting of medical histories of kindred members from five generations. SETTING: Outpatient General Clinical Research Centers and patients' homes. MEASUREMENTS: Screening was done while patients were on a self-selected diet and included blood pressure determinations; serum potassium and plasma renin activity and aldosterone measurements; and 24-hour urinary tetrahydroaldosterone, 18-oxotetrahydrocortisol, and 18-hydroxycortisol measurements. RESULTS: Diagnosis of GRA was established on the basis of a previously described specific biochemical abnormality, overproduction of the cortisol C-18 oxidation products (18-oxotetrahydrocortisol and 18-hydroxycortisol) in urine and their ratio relative to tetrahydroaldosterone. Glucocorticoid-remediable aldosteronism was diagnosed in 11 additional patients spanning three generations; this group included the youngest patient (3 months old) ever diagnosed with GRA. Complete penetrance of the biochemical abnormality is likely, with 11 of 18 at-risk patients displaying the phenotype. All patients with GRA had elevated blood pressure. Affected adult patients had been diagnosed as hypertensive before reaching 21 years of age (n = 7 mean, 16.1 +/- 3.4 years). All affected patients were normokalemic (4.3 +/- 0.3 mmol/L). CONCLUSION: Hypertension is a characteristic feature of GRA. Elevated blood pressure in this kindred developed at an early age and often was severe. Because a normal potassium level does not exclude the diagnosis of GRA, the disorder may be underdiagnosed. The value of a specific cortisol C-18 oxidation phenotype in the diagnosis of GRA has been confirmed.

Adolescent↗
PubMed1992

A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.

Base Sequence↗
PubMed1992

Impact of the Los Angeles County Trauma System on the survival of seriously injured patients.

We compared the survival of 658 seriously injured patients treated in Los Angeles County in the Fall of 1982 (prior to the activation of the trauma system) with that of 766 such patients treated in the Fall of 1984 (when the system was young and composed of essentially a full complement of trauma centers). We demonstrated a statistically significant improvement in the adjusted odds of survival for 1984 over 1982 with regard to victims of motor vehicle collisions who sustained multiple serious injuries (1980 Injury Severity Score: 26-50) (p = 0.042). For the data set as a whole, although an improvement in survivorship over this period was suggested by the data, statistical significance could not be demonstrated.

Adolescent↗
PubMed1992

The effect of immunosuppression on the development of cerebral oedema in an experimental model of intracerebral haemorrhage: whole body and regional irradiation.

The oedema which forms around an intracerebral haemorrhage has a complex aetiology. The immune response may have a role in its formation. There is clinical and experimental evidence that circulating leucocytes and platelets may mediate oedema formation. Global depletion of circulating leucocytes and platelets by whole body irradiation in a rodent model of intracerebral haemorrhage was found to confer protection against both ischaemia and oedema formation. This was not a direct effect of irradiation of the brain. The possible mechanisms for this protection are discussed.

Animals↗